Daiichi Sankyo Company (4568) WCLC/ESMO 2024 Conference summary

Conference overview

• The event highlighted recent data from WCLC and ESMO 2024, focusing on progress in the DXd ADC portfolio and emerging next-generation ADCs.

• Presentations covered updates in lung, ovarian, endometrial, and breast cancers, with emphasis on new standards of care and innovation for patients.

• Key studies included TROPION-Lung01, NeoCOAST-2, TROPION-PanTumor03, DESTINY-Lung03, and early data on DS-9606.

• Multiple oral presentations at WCLC 2024 highlighted new data from pivotal lung cancer trials, including TROPION-Lung01, DESTINY-Lung03, NeoCOAST-2, and IDeate-Lung01.

• The Q&A session addressed regulatory, biomarker, and strategic questions from investors and analysts.

Key clinical trial results and study updates

• TROPION-Lung01: Dato-DXd showed statistically significant PFS but not OS in second-line non-small cell lung cancer, with benefit most pronounced in non-squamous patients and a manageable safety profile.

• DESTINY-Lung03: T-DXd showed a 44.4% response rate and median PFS of 8.2 months in HER2-overexpressing NSCLC, with higher responses in IHC 3+ and EGFR TKI pretreated patients.

• NeoCOAST-2: Dato-DXd plus durvalumab and chemotherapy in resectable NSCLC led to the highest pCR (34.1%) and mPR (65.9%) rates among tested regimens, with manageable safety and high surgical feasibility.

• IDeate-Lung01: I-DXd (B7-H3-DXd) in small cell lung cancer showed higher efficacy at 12 mg/kg (54.8% response rate), with rapid, durable responses and tolerable safety.

• TROPION-PanTumor03: Dato-DXd monotherapy demonstrated encouraging efficacy in pretreated ovarian and endometrial cancers.

• HER3-DXd in advanced HR+ HER2- breast cancer showed a 53.5% response rate and manageable safety in a heavily pretreated population.

• DS-9606 (claudin 6 ADC): Early phase I data showed manageable safety and preliminary anti-tumor activity, especially in germ cell tumors.

Biomarker and technology advancements

• Quantitative Continuous Scoring (QCS) for TROP2 normalized membrane ratio is a promising predictive biomarker for Dato-DXd efficacy in NSCLC, with QCS-NMR+ patients experiencing longer PFS and higher ORR.

• DESTINY-Lung03 reinforced HER2 IHC as an actionable biomarker in NSCLC, supporting routine HER2 testing for patient selection.

• Biomarker positivity was higher in non-squamous than squamous NSCLC, potentially explaining differential efficacy.

• Ongoing efforts include expanding biomarker strategies beyond QCS, with collaborations and technology development in digital pathology and genomics.

• NeoCOAST-2 results suggest ADC-based combinations may enhance pathological response rates regardless of baseline PD-L1 status.